Expert Point of View: Antonio Llombart-Cussac, MD, PhD

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Discussant of the abstracts, Antonio Llombart-Cussac, MD, PhD, of Hospital Arnau de Vilanova, Universidad Catolica Valencia, Spain, noted that establishing these regimens in the third-line setting of metastatic disease and beyond will require demonstration of consistent gains in both progression-free and overall survival, as well as activity in patients with brain metastases. In addition, he added, balancing quality of life with drug activity will play an important role in the decision process along with the identification of treatment-driven biomarkers.

According to Dr. Llombart-Cussac, selection criteria in the past excluded patients with specific brain scenarios, although not necessarily those with the worst prognosis. The HER2CLIMB trial was critical, he said, because many patients on study had brain disease progression at the time of enrollment. Nevertheless, the activity demonstrated in patients with brain metastases did not differ significantly from that in the overall population.

“With progression-free survival increasing by almost 2 months in patients with brain metastases on tucatinib, brain metastasis is no longer a limitation nor a contraindication but rather even a good indication for this combination regimen,” noted Dr. Llombart-Cussac. “With solid overall survival gains and no major toxicity or quality-of-life concerns, tucatinib in combination with trastuzumab and capecitabine will become the new standard third-line treatment,” he predicted.

‘Astonishing’ Activity With T-DXd

With regard to the DESTINY-Breast01 study, Dr. Llombart-Cussac said fam-trastuzumab deruxtecan (T-DXd) has the potential to change paradigms of treatment, but interstitial lung disease risk, prevention, and management should be well characterized before moving to earlier lines of treatment or considering it standard for all patients. However, he called the activity of the agent “astonishing.”

Although future trials, such as DESTINY-Breast02 and DESTINY-Breast03, will enlarge the inclusion criteria for patients with brain disease, said Dr. Llombart-Cussac, specific trials need to be designed to define the best approaches for different scenarios of brain involvement. 

DISCLOSURE: Dr. Llombart-Cussac reported financial relationships with MedSIR, Initia-Research, Eisai, Celgene-BMS, Lilly, Pfizer, Roche, Novartis, MSD, Tesaro-GSK, Roche, Pierre Fabre, Genomic Health, AstraZeneca, Foundation Medicine, and Agendia.

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